封锁
医学
CD8型
肺癌
肿瘤科
内科学
PD-L1
细胞毒性T细胞
队列
免疫学
流式细胞术
免疫疗法
免疫系统
T细胞
生物
受体
体外
生物化学
作者
Chang Gon Kim,Min Hee Hong,Kyung Hwan Kim,In-Ho Seo,Beung‐Chul Ahn,Kyoung‐Ho Pyo,Chun‐Bong Synn,Hong In Yoon,Hyo Sup Shim,Yong Il Lee,Seong Jin Choi,Yun Jeong Lee,Ellen Janine Kim,Youngun Kim,Jeong-Eun Kwak,Jinkyung Jung,Su–Hyung Park,Soonmyung Paik,Eui‐Cheol Shin,Kyoung‐Ho Pyo
标识
DOI:10.1016/j.ejca.2020.10.028
摘要
Background The predictive value of immune monitoring with circulating CD8+ T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1+CD8+ T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade. Methods Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8+ T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1+CD8+ T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119). Results Circulating PD-1+CD8+ T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1+ cells among CD8+ T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8+ T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8+ T lymphocytes suppresses the effector functions of tumour antigen-specific CD8+ T lymphocytes. Conclusions Dynamic changes in circulating PD-1+CD8+ T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors.
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